Propofol 1% emulsion (10 mg/mL; Novopharm Ltd, Toronto, Canada, lot 06K325, expiry August 2008) was combined in a ratio of either 50:50 or 70:30 with ketamine solution (10 mg/mL; Sandoz Inc, Boucherville, Quebec, lot 132425). Ten-millilitre samples of the mixture were then trans­ferred to each of three 20-mL polypropylene syringes (Becton Dickinson and Company, Franklin Lakes, New Jersey), which were sealed with syringe caps (Baxa Corporation, Markham, Ontario, reference number 66001). The syringes were stored at room temperature (23°C) with exposure to light.

Physical Evaluation

At each measurement time, the pH was measured, in duplicate, with a calibrated pH meter (Accumet model 25, Fisher Scientific Co, Ottawa, Ontario). Buffer 4 (Fisher Scien­tific, lot SC6236793, expiry September 30, 2008) and buffer 7 (Fisher Scientific, lot SC7134746, expiry May 12, 2009) were used to calibrate the pH meter initially. The emulsions were observed under illuminated 4 x magnification for signs of separation, cracking, gas production, and colour change against a black background. An unopened vial of propofol 1% emulsion was used as a colour control. Visual inspections were conducted by a single observer (R.F.D.).buy viagra jelly

A previously published method was used for analyzing propofol. A mobile phase containing acetonitrile— methanol—water (55:10:35) was pumped first through a C18 guard column (Phenomenex Inc, Torrance, California, catalogue number AJO-4287) and subsequently through a C18 analytical column (Luna 5 ^m 4.6 mm x 250 mm column; Phenomenex Inc, lot 365391-1) at 1 mL/min. Elution of 50-^L samples was monitored at 270 nm. Thymol (1 mg/mL in water; Sigma Aldrich Co, St Louis, Missouri) was used as an internal standard. The method was determined to be stability- indicating by following forced degradation samples over 146 h. The pH of a 10-mL sample of propofol 1% emulsion (Novopharm Ltd, lot 06K325, expiry August 2008) was adjust­ed to about 1.2 with concentrated hydrochloric acid (BDH Inc, Toronto, Ontario, lot 120834), while another 10-mL sample was adjusted to a pH of about 12.0 with sodium hydroxide 5N solution (Fisher Scientific, lot SC6135444, expiry May 31, 23008).canadian pharmacy viagra

These degradation solutions were heated to 50°C in a hot water bath, and multiple samples were tested over 146 h. Validation consisted of completion of a standard curve over the concentration range of 0.01 to 0.05 mg/mL, a recovery study, and determination of intraday variance at 0.03 mg/mL. A standard stock solution was prepared by diluting commercially available propofol 1% emulsion (Novopharm Ltd, Toronto, Ontario, lot 06K326, expiry October 2008) with acetonitrile-methanol-water (55:10:35) to 0.1 mg/mL. The standard stock solution was further diluted to 0.01, 0.02, 0.03, 0.04, and 0.05 mg/mL with acetonitrile-methanol-water (55:10:35) after the addition of 50 ^L of internal standard. The recovery solution was prepared in the same manner as the 0.03 mg/mL standard solution except that the initial propofol 1% emulsion was the same lot as that used for the test solutions. Intraday testing was based on 5 replicate injections completed at 3 separate time points (0, 4, and 14 h). Peak purity was assessed through multiple- wavelength (220 and 270 nm) and ultraviolet (UV) spectral analysis (206-350 nm) and visual monitoring of peaks for change in shape.generic viagra online

Analysis of the ketamine used a previously validated HPLC method,11 which consisted of mobile phase containing 25% acetonitrile, 0.1% phosphoric acid, 85% sodium dodecyl sulfate 1.6 mmol/L, and 0.3% dibutylamine 0.5 mol/L, with final pH adjusted to 5.0. The mobile phase was pumped through a 5-^m, C 4.6 x 250 mm column (Luna ODS 18(2), Phenomenex Inc, lot 410754) at a rate of 1.0 mL/min. Peaks were monitored at 270 nm after injection of 50-^L samples. Phenol (0.3 mg/mL; Fischer Scientific, lot 026530) was used as the internal standard. The peak purity of ketamine peaks was determined through the use of multiple- wavelength (270 and 254 nm) and UV spectral analysis (200-350 nm). The UV spectral comparison of ketamine peaks from degraded samples with the ketamine reference material was completed, and correlation coefficients were calculated. Intraday variation was calculated from 5 replicate injections at 3 separate time points. Recovery samples were run concurrently on those days. The linearity of all standard curves was assessed by least-squares regression analysis. Samples containing ketamine-propofol were tested using this method to determine if there were any interfering peaks from the propofol or other excipients.

Immediately after preparation of the test mixtures, as described above, a 2-mL sample from each syringe was filtered through a 0.2-^m polytetrafluoroethylene filter (PTFE, Millipore, Carrigtwahill, Ireland, catalogue number SLLG025SS) into clean glass test tubes. The filtered samples were then diluted either 1:50 (for the 50:50 mixture) or 1:100 (for the 30:70 mixture) with 100% acetonitrile, and 300 ^L of the resulting solution was combined with 50 ^L of internal standard and 650 ^L of the mobile phase. These samples were then assayed in duplicate (n = 6). The filtration and analysis steps were repeated at 1 and 3 h after preparation.Cialis Jelly

The rationale for filtering the solutions was to remove any precipitate that might have formed and that was not visible but that could be redissolved when diluted with 100% acetonitrile. The effect of filtering the mixture were also studied by assaying solutions of propofol both before and after filtration.

Solutions were considered stable if both drug concentra­tions remained above 90% of the original value.